The overall objective of this research project is to establish the mechanism(s) whereby adoptive immunotherapy in combination with chemoradiotherapy is able to prolong survival rates and prevent development of recurrent leukemia. An experimental treatment model using allogeneic bone marrow transplantation and chemoradiotherapy for the treatment of advanced spontaneous leukemia in mice has been developed. The unique feature of the treatment model is the use of gnotobiotic techniques (intestinal decontamination and isolation in a protective environment) to prevent secondary disease. This experimental model is being used to examine questions regarding the relative importance of chemoradiotherapy in reducing the tumor burden which adoptive immunotherapy must eliminate, the nature of the effector cells involved in an adoptive immunotherapeutic reaction, the evolution of antihost and antitumor reactivity in allogeneic chimeras and the immune competence of leukemia-cured chimeras. Information obtained from these studies should contribute to an understanding of the complex events taking place in tumor-bearing animals following allogeneic bone marrow transplantation.